Interleukin-22 (IL-22), also known as interleukin-10 related T cell-derived inducible factor (IL-TIF), is a glycoprotein secreted by T cells. The expression of IL-22 mRNA was originally demonstrated in IL-9-stimulated T cell lines, IL-9-stimulated mast cell line, as well as concanavalinA activated spleen cells of mouse. The human IL-22 mRNA is mainly expressed in isolated peripheral T cells and are upon stimulation by anti-CD-3 antibody or ConA. IL-22 mRNA is also expressed in the stimulated NK cells. Activated T cells are mainly CD4+ cells, especially Th1 cells via the CD28 pathway.
IL-22 precursor is composed of 179 amino acid residues (the mature peptide is composed of 146 amino acid residues). Dumoutier et al. first reported the cloned IL-22 genes of mouse and human (Dumoutier, et al., JI 164:1814-1819, 2000). In addition, Dumoutier obtained patents related to IL-22 (U.S. Pat. No. 6,359,117 and U.S. Pat. No. 6,274,710), whereas Gurney obtained a patent related to use of IL-22 in the treatment of human pancreatic disease (U.S. Pat. No. 6,551,799).
IL-22 is mainly expressed in thymus, brain, activated T cells and mast cells, the lectin-stimulated spleen cells (Duroutier JI 2002), interleukin-2/interleukin-12-stimulated NK cells (Wolk, K JI 2002), and in a number of organs and tissues, including gut, liver, stomach, kidney, lung, heart, thymus, and spleen, upon LPS stimulation (Dumoutier PNAS paper), in which an increase of the expression of IL-22 in those organs and tissues can be measured.
IL-22 exerts its biological function by binding IL-22R1 receptor and IL-10R2 receptor. IL-22R1 is a receptor specific to IL-22 and is expressed in skin, kidney, the digestive system (pancreas, small intestine, liver, large intestine, colon), and the respiratory system (lung, bronchi). The research on IL-22 as a regulatory agent to the immune system has been published. The medical use of IL-22 in reducing serum triglycerides and obesity has been reported in patent applications related to the medical uses of IL-22 (See WO 2006/073 508 and CN 200510023103.0). However, it has not yet been discovered that IL-22 can play an active role in the treatment of nerve damage diseases or neurodegenerative diseases.
Neurodegenerative disease is a condition of progressive degeneration and death of neurons in brain and spinal cord. It is a kind of chronic and progressive disease of the nervous system, mainly including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease, amyotrophic lateral sclerosis, spinal muscular atrophy, and spinal cerebellar ataxias, etc. These neurological diseases are characterized by a common feature of degeneration and apoptosis of neurons, which result in the abnormal behavior and dysfunction of patients, and lead to a premature death. The pathogenesis of neurodegenerative diseases remains obscure, as yet no existing effective method and medicine are available. Current treatments for PD comprise the replenishment of neurotransmitters in patients' brain via oral administration or intravenous injection, such as levodopa, whereas levodopa cannot effectively control the naturally pathogenic progression of PD and cannot affect the speed of degeneration of dopaminergic neurons. Moreover, long-term use of levodopa brings a variety of adverse side effects, such as on-off phenomenon and dyskinesia, and its therapeutic effects only last about 2 years. Long-term use of levodopa may cause neuronal damage as well as speeding up apoptosis of the neurons. Current treatments for AD comprise increasing the concentration of acetylcholine directed against the deficiency of acetylcholine in AD patients' brain using choline esterase inhibitors. This method is only symptomatic treatment and cannot control the development of the disease, either.
Therefore, there is an urgent need in the art to develop more effective drugs or methods for treatment and prevention of nerve damage diseases or neurodegenerative diseases.